Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant
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Published:2010-06-15
Issue:12
Volume:84
Page:5975-5985
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ISSN:0022-538X
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Container-title:Journal of Virology
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language:en
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Short-container-title:J Virol
Author:
Barnett Susan W.1, Burke Brian1, Sun Yide1, Kan Elaine1, Legg Harold1, Lian Ying1, Bost Kristen2, Zhou Fengmin1, Goodsell Amanda1, zur Megede Jan1, Polo John1, Donnelly John1, Ulmer Jeffrey1, Otten Gillis R.1, Miller Christopher J.2, Vajdy Michael1, Srivastava Indresh K.1
Affiliation:
1. Novartis Vaccines and Diagnostics, 350 Massachusetts Avenue, Cambridge, Massachusetts 02139 2. California National Primate Research Center, University of California, Davis, California
Abstract
ABSTRACT
We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV
SF162P4
following sequential immunization with alpha
v
irus
r
eplicon
p
articles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1
SF162
gp140ΔV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV
SF162P4
(intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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